Immunoglobulin E autoantibodies in atopic dermatitis associate with Type‐2 comorbidities and the atopic march

Abstract

BackgroundAutoreactive immunoglobulin E (IgE) antibodies to self‐peptides within the epidermis have been identified in patients with atopic dermatitis (AD). Prevalence, concomitant diseases, patient characteristics, and risk factors of IgE autoantibody development remain elusive. We aimed to determine IgE autoantibodies in serum samples (n = 672) from well‐characterized patients with AD and controls (1.2–88.9 years).MethodsAtopic dermatitis patients were sub‐grouped in AD with comorbid Type‐2 diseases (“AD + Type 2”; asthma, allergic rhinitis, food allergy, n = 431) or “solely AD” (n = 115). Also, subjects without AD but with Type‐2 diseases (“atopic controls,” n = 52) and non‐atopic “healthy controls” (n = 74) were included. Total proteins from primary human keratinocytes were used for the immunoassay to detect IgE autoantibodies. Values were compared to already known positive and negative serum samples.ResultsImmunoglobulin E autoantibodies were found in 15.0% (82/546) of all analyzed AD‐patients. “AD + Type 2” showed a higher prevalence (16.4%) than “solely AD” (9.6%). “Atopic controls” (9.6%) were comparable with “solely AD” patients, while 2.7% of healthy controls showed IgE autoantibodies. Of those with high levels of IgE autoantibodies, 15 out of 16 were patients with “AD + Type 2”. AD patients with IgE autoantibodies were younger than those without. Patients with IgE autoreactivity also displayed higher total serum IgE levels. Factors that affected IgE autoantibody development were as follows: birth between January and June, cesarean‐section and diversity of domestic pets.ConclusionsImmunoglobulin E autoantibodies in AD seem to associate with the presence of atopic comorbidities and environmental factors. The potential value of IgE autoantibodies as a predictive biomarker for the course of AD, including the atopic march, needs further exploration.

Biomarkers for phenotype-endotype relationship in atopic dermatitis: a critical review

“…A recent study suggests that immunoglobulin E (IgE) autoantibodies could be biomarkers for AM. 65 This cross-sectional study found that AD patients with other type 2 comorbidities had higher levels of autoreactive IgE compared to those with only AD. Notably, a significant majority of AD patients with elevated autoreactive IgE also had type 2 comorbidities.…”

“… 48 Also, sensitization to self-proteins has been thought to cause AD, which is distinct from the classic AD clinical phenotype. 65 Nonetheless, the utility of these biomarkers is viewed differently in clinical trials and clinical settings, since the clinical efficacy of particular therapies for AD is best measured by clinicians and patients through visual assessments.…”

“… 73 Oxidative stress markers Increased malondialdehyde Increased urinary 8-hydroxy-2′-deoxyguanosine Increased urinary acrolein-lysine Increased bilirubin oxidative metabolites Increased disulfide/total thiol ratio Decreased native thiol/total thiol ratio Increased LTB4 in exhaled breath condensate Increased 8-isoprostane in exhaled breath condensate Decreased pH in exhaled breath condensate 74 , 75 , 76 , 77 VEGF Increased serum VEGF level at three years 78 IL-13 Increased serum IL-13 level 79 GWAS with unsupervised modeling Black race: chromosome 2–rs60242841; AD to AA White race–male/female: chromosome 13–rs9565267; AD to AR White race–male: chromosome 4–rs 151041509; AD to AR White race–female: chromosome 17–rs 78171803; AD to AR Asian race–female: no associated SNP; AD to FA 80 Immunoglobulin E (IgE) autoantibody AD patients with AA or AR or FA showed higher prevalence of IgE autoantibodies. AD patients with IgE autoantibodies were younger, and displayed higher total serum total IgE level 65 FABP5, fatty acid binding protein 5; AD, atopic dermatitis; AM, atopic march; LTB4, leukotriene B4; VEGF, vascular endothelial growth factor; GWAS, genome-wide association; AA, allergic asthma; AR, allergic rhinitis; FA, food allergy. …”

Autoreactive IgE: Pathogenic role and therapeutic target in autoimmune diseases

“…The evaluation of studies with a sample size greater than 100 showed a range of 23%–28% in eczema patients 98 . A recent study including 672 subjects found a prevalence of 16.4% in patients with AD and atopic comorbidities, 9.6% in patients with solely AD, 9.6% in atopic controls without AD, and 2.7% in non‐atopic subjects 99 …”

“…98 A recent study including 672 subjects found a prevalence of 16.4% in patients with AD and atopic comorbidities, 9.6% in patients with solely AD, 9.6% in atopic controls without AD, and 2.7% in nonatopic subjects. 99 The levels of IgE AAb in AD patients are correlated with disease severity. 84,89,91,93,[100][101][102] Therefore, it is held that their presence is clinically relevant, but their precise pathophysiological contribution still requires further investigations.…”